Sandbox 49

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=Trypsin= Trypsin is a serine protease that is produced in the pancreas as the inactive proenzyme trypsinogen. It hydrolyses proteins (peptide bonds) and it is found in many vertebrates. Trypsin cleaves peptide chains mainly at the carboxyl (red) side of the amino acids lysine or arginine, except when either is followed by proline. The German physiologist Wilhelm Kühne (1837-1900) discovered trypsin in 1876.

Structure
The primary structure of trypsin contains ~240-residue enzymes. The secondary structure of trypsin contains both alpha helices, highlighted in blue and beta sheets , highlighted in green. The backbone, also known as the main chain, is the protein and nucleic acid chain that makes up trypsin (blue chain). The amino (N) to carboxy (C) terminal can be seen beginning at the blue 5' terminal to the red 3' terminal. Trypsin contains a catalytic triad consisting of the residues histidine, aspartate and serine. Histidine and serine are located in the enzyme-substrate binding site and aspartate is located in a nearby solvent-inaccessible pocket. Serine exists as the nucleopihilic active site due to the charge created by the formation of these residues. Trypsin is referred to as an endopeptidase, as it cleaves within a polypeptide chain rather than at the terminal amino acids at the ends. The reaction mechanism of tryspin can be seen to the right. The transition state is thought to be stabilized by an unusually strong hydrogen bond and is the location of preferential binding.

Polarity
The polarity of trypsin can be seen with purple representing polar areas and gray representing nonpolar areas. It can be seen that mostly hydophilic (purple) residues exist on the outside of the molecule while hydrophobic (gray) residues are located mostly on the inner parts of the molecule. The hydrophobic areas do not favor interaction with an aqueous environment and therefore confine themselves closer to the center of the molecule. The side chains, which are the basis for determining the polarity of trypsin, are represented by the green wire frames. They are composed of several different amino acids with a variety of charges.

Molecular Attractions
The overall charge of trypsin is observed with red showing the negative charges (anionic) and blue showing the positive charges (cationic), while purple shows the uncharged areas. The charged portions of trypsin can be seen on the outside of the molecule in order to increase attraction forces. Trypsin can be seen interacting with three different elements including oxygen(red), sodium (blue) and sulfur (yellow). In trypsin (as in all proteins), salt bridges occur between amino acid side chains with opposite positive or negative full-electron charges, namely, (at neutral pH) Glu- or Asp- vs. Arg+ or Lys+. A salt bridge found in trypsin can be seen to the right.

Intermolecular Forces
The ligands found in trypsin are composed of oxygen(red) and sulfur (yellow). Trypsin contains four ligands and these are the areas where intermolecular forces occur, including van der Waals forces, ionic bonds and hydrogen bonds. These forces allow trypsin to bind with other molecules in order to carry out a certain process. Trypsin is active against only the peptide bonds in protein molecules that have carboxyl groups donated by the positively charged amino acids arginine and lysine (seen to the right), which are stabilized and attracted by aspartate, leading to enzyme specificity. Water is an example of the van der Waals forces that are occurring with trypsin. Only a small amount of the water binds tightly enough to be seen, whereas there is much more in actuality surrounding trypsin but cannot be seen due to disorder. Trypsin is a hydrolase and cleaves bonds by hydrolysis at the peptide bonds. DNA can interact with the alpha helices and DNA can also interact with the beta sheets (nucleotide interactions).

Involvement in disease
One consequence of the autosomal recessive disease cystic fibrosis is a deficiency in transport of trypsin and other digestive enzymes from the pancreas. Cystic Fibrosis (CF) is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator. This gene is needed to control the amount of sweat, digestive juices, and mucous the body makes. CF is a common disease which affects the entire body, causing progressive disability and often early death. The name cystic fibrosis refers to the characteristic scarring or fibrosis and cyst formation within the pancreas. The most serious symptom is difficulty breathing caused by repetitive lung infections. A picture of a normal airway compared to an airway with cystic fibrosis can be seen to the right. The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as an exocrine gland, secreting pancreatic juice containing digestive enzymes that pass to the small intestine. This disease can lead to meconium ileus which involves an intestinal obstruction (ileus) due to thick meconium which is normally broken down by trypsins and other proteases, then passed in feces. Meconium is the earliest stool of an infant which is composed of materials ingested during the time the infant spends in the uterus such as intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. Meconium is quite sterile and it is normally broken down by trypsin and other proteases, then passed in the feces.